To Find the Physiology

A New Era for Research

Research into mental disorders hopes to identify the underlying physiological conditions that cause them. Recent research tells us that the neurocircuits which express behavior do not fit within the conceptual boundaries defined by our current diagnostic system. It would be very inefficient if every time we needed to respond to something, the brain had to gear up ten or twenty separate functions. Instead, our highly efficient and complex brains necessarily integrate a slew of causes and effects that feed both forward and/or back in every action they initiate. And, importantly, this integration has evolved with one basic goal in mind; survival.

To conceptually separate behavioral and physical symptoms into different categories and then pursue research based on those categories is not likely to reveal a meaningful physiological picture. If effective and targeted treatments rely upon understanding the physiology which causes impairment in behavior, then it is essential to reframe how we consider the disorders.

Stepping into the New Era

In addition to the pressure that advancements in neurology have imposed on the credibility of the existing classification system, the troubling rate of co-morbidity has also raised a red flag. The coupling of mental disorders occurs more often than can be explained by chance if the disorders were properly defined. In comparison, multiple diagnoses are not the norm in the field of medicine.

These concerns, supported by the advancements in the field of neurology, have initiated a shift in the psychiatric field. The new Diagnostic and Statistical Manual scheduled for release in 2013 has incorporated several changes in order to learn more about the overlapping nature of the disorders as well as to better consider the degrees of severity of symptoms within those disorders

In 2009, the National Institute for Mental Health (NIMH) initiated a research directive that will gather information to build a base of knowledge that will help us to better understand how our brains work, and therefore, how our behaviors are created and changed due to pathophsyiology. They plan to fund research that falls under several broad domains of behavior and which seeks to learn about the genes, molecules, cells, circuits, physiology, behavior, self reports and paradigms in each of those domains.

JBRF Research Consortium and the New Era

Research pursued by the JBRF Research Consortium reflects the field’s forward movement. Dimensional analysis by the Consortium of symptom data from thousands of children at risk for, or with a diagnosis of, bipolar disorder led to the identification of a complex, evolutionarily ancient pathway that ties together the physical and the behavioral and cuts across classification boundaries that are currently established. (Click here to read From Trait to Treatment.)

The pathway at the base of the hypothesis is called the orexigenic neuropeptide pathway. This pathway uses a class of transmitters called orexins, which, either directly or indirectly, integrate very basic homeostatic systems of survival: temperature regulation, metabolic signals, and arousal, as well as all the downstream behaviors and responses which support those systems. Downstream effects would include everything from blood pressure and shivering to reward seeking and eating, to fear response and sleeping, and so much more. Briefly, disruption of that pathway can explain the broad range of symptoms that plague many of the children who are diagnosed with bipolar disorder.

Through their research, investigators have discovered that thermal regulation plays an important role in the expression of the behaviors and symptoms experienced by the children whose data they studied. Thermoregulation is not a domain typically considered in the field of psychiatry. However, investigators have come to consider it a crucial component of the condition.

Tracing the neural networks of this pathway has demonstrated the extraordinary complexity, and far reaching effect, of a single pathway. It logically brings together symptoms and behaviors that would never before have been associated with each other. The further the pathway is traced, the more parsimonious the explanation becomes. This, of course, reflects the beautiful efficiency of nature.

The utility of the hypothesis is strengthened by the fact that a treatment which is known to directly and predictably affect that network has resulted in a dramatic and sustained reversal of symptoms. This is the gold standard of medical research.

From here…

There continues to be much to discover about this illness. In addition to learning more about the role of thermoregulation to this disorder, the investigators have already identified several other areas that deserve further inquiry. Notably, the hypothesis tells them that they must learn more about the neural mechanisms which interpret circadian and circannual signals from the environment as these inputs have a prominent influence on the orexigenic pathway.